Hendra virus is the source of a recently emerging disease in animals and human. Hendra virus was first recognized in September 1994 after an outbreak of respiratory illness among twenty horses and two humans in Hendra, Queensland, Australia (Selvey L A, et al., Med J Australia 1995, 162:642-5). Thirteen horses and one human died. In 1995, a second unrelated outbreak was identified that had occurred in August 1994 in Mackay, Queensland, in which two horses died and one human became infected (Hooper P T, et al., Australian Vet J 1996; 74:244-5; Rogers R J, et al., Australia Vet J 1996; 74:243-4). Four of the seven people who contracted the virus from infected horses have died since the disease first emerged in 1994. The fatality rate has been reported at more than 70% in horses and 50% in humans.
Nipah virus is a member of the Paramyxoviridae family and is related to the Hendra virus (formerly called equine morbillivirus). The Nipah virus was initially isolated in 1999 upon examining samples from an outbreak of encephalitis and respiratory illness among adult men in Malaysia and Singapore (see, e.g., Chua et al., Lancet. 1999, 354 (9186):1257-9 and Paton et al., Lancet. 1999 Oct. 9; 354(9186):1253-6). The host for Nipah virus is still unknown, but flying foxes (bats of the Pteropus genus) are suspected to be the natural host. Infection with Nipah virus in humans has been associated with an encephalitis characterized by fever and drowsiness and more serious central nerve system disease, such as coma, seizures and inability to maintain breathing (see, e.g., Lee et al., Ann Neurol. 1999 September; 46(3):428-32). Illness with Nipah virus begins with 3-14 days of fever and headache, followed by drowsiness and disorientation characterized by mental confusion. These signs and symptoms can progress to coma within 24-48 hours. Some patients have had a respiratory illness during the early part of their infections. Serious nerve disease with Nipah virus encephalitis has been marked by some sequelae, such as persistent convulsions and personality changes. During the Nipah virus disease outbreak in 1998-1999, about 40% of the patients with serious nerve disease who entered hospitals died from the illness (see, e.g., Lam & Chua, Clin Infect Dis. 2002 May 1; 34 Suppl 2:S48-51).
Hendra virus, like the majority of other paramyxoviruses, possess two surface glycoproteins, a fusion protein (F) and an attachment protein (G), that are involved in promotion of fusion between the viral membrane and the membrane of the target host cell. Hendra and Nipah viruses require both their attachment and fusion proteins to initiate membrane fusion (Bossart et al., J Virol. 2002; 76:11186-98). Various studies were conducted to understand the functions of the G and F proteins in virus infection. A soluble G glycoprotein of Hendra virus was constructed and showed the capability to bind to Hedra virus and Nipah virus infection-permissive cells (Bossart et al., J Virol. 2005; 79:6690-6702). Monoclonal antibodies specific for the Nipah virus fusion protein were shown to neutralize Hedra virus in vitro and protected hamsters from Hendra virus (Guillaume et al., Virology 2009; 387:459-465). A recombinant soluble Hendra G protein in CpG adjuvant was evaluated in a cat model (McEachern et al., Vaccine 2008; 26:3842-3852).
Currently there is no licensed Hendra vaccine. Therefore, there is a general need for a Hendra vaccine for the protection against Hendra virus and Nipah virus infection, prevention of the disease in animals and human and prevention of spreading of the virus to uninfected animals or human.
The invention provides a solution for optimizing the immunological and efficacious effect of Hendra virus vaccine while retaining high safety for the vaccinated animals.